Individuals diagnosed with schizophrenia have a 2.8 to 3.5 increased likelihood over that of the general population of being obese (body mass index of 30 or higher) ⁶. Both women and men with schizophrenia develop a central form of obesity with enlarged waist circumferences ⁷.

Because the spike in obesity in this population correlates in time with the introduction of second-generation antipsychotic drugs, these agents are rightly considered to be major causal contributors to the phenomenon. During the same time period, however, obesity rates also rose in the general population not because of drugs but because of the proliferation and ready availability of calorie-rich foods and an increasingly sedentary urban lifestyle ^{8, 9}. The Noncommunicable Disease ¹⁰ Risk Factor Collaboration of the World Health Organization pooled 1698 population-based studies consisting of more than 19 million participants and found that, from 1975 to 2014, the age-corrected mean body mass index (BMI) rose from 21.7 to 24.2 in men, with a slightly lesser rise in women. There are approximately 8% more obese individuals in the world today than there were 40 years ago ¹⁰. Although many of the very poor across the world continue to be undernourished, obesity is prevalent even among this demographic because healthy foods cost more than calorie-rich food. This is very relevant to individuals with schizophrenia who are among the poorest poor – due to several well-known factors such as the severity and chronicity of the symptoms (false perceptions, false beliefs, lack of motivation, cognitive defects) associated with this illness, the unemployment that results from both illness and interrupted schooling, and the direct costs of the illness, its treatment, and its long years of rehabilitation ¹¹. Over the years of illness, people with schizophrenia drift downwards in socioeconomic class ¹² and end up living in disadvantaged neighborhoods where high calorie food is more affordable than low calorie food and where there are few opportunities for physical activity and energy expenditure. The neighborhoods in which people with schizophrenia live are crowded, violent, and dangerous ¹³, discouraging residents from even stepping outside the home, never mind walking or jogging ¹⁴. In addition, ‘negative’ symptoms such as apathy and asociability are characteristic of approximately 60% of individuals with schizophrenia, which means that people with this diagnosis prefer lonely, sedentary activity such as napping or watching TV to engaging in more vigorous weight-losing activities, especially when these involve other people ^{15, 16, 17}. One study found that 81% of time spent by people with schizophrenia was sedentary time ¹⁷.

Twenty-five percent of people with schizophrenia are said to be depressed ¹⁸, which makes a passive, isolated, obesity-prone lifestyle even more likely. In order, perhaps, to stay away as much as possible from other people, patients with schizophrenia may reverse day and night, sleep during the day and, at night, have little to do but eat ¹⁹.

Another factor is alcohol. Forty percent of men with schizophrenia and 23% of women patients are addicted to alcohol, usually in the form of beer, which is particularly calorigenic ²⁰. More than 60% smoke heavily ²¹ and when they stop (smoking cessation programs are part of comprehensive care for patients with schizophrenia), they gain weight ²².

Although nutrition guidance is also part of comprehensive treatment, the low calorie diets recommended by dieticians are not only unaffordable but, in addition, require more preparation than ready-made food – a culinary effort that is difficult for people with severe psychotic symptoms to undertake. Despite guidance, patients with schizophrenia continue to eat fatty foods, few fruit and little fiber ^{23, 24, 25}.

In recent years, it has been recognized that the same genes may confer risk to different diseases. For instance, for most gene regions that have been linked to schizophrenia, overlapping regions of linkage have also been obtained in type 2 diabetes ²⁶. Understanding copy number variations (CNVs) in the genome has opened up new mechanisms by which a genetic variation can affect more than one phenotype. In the last 5 years, an increasing number of studies have found that individuals who have micro-duplications at the 600-kilobase break points 4 and 5 near the middle of chromosome 16, at a location designated p11.2, have an increased risk of psychotic disorders ²⁷. A meta-analysis reports a fourteen fold-increased risk of psychosis and a sixteen fold increased risk of schizophrenia in individuals with micro-duplication at proximal 16p11.2 ²⁸. These same CNVs are associated with decreased body mass while microdeletions in this region are associated with obesity ²⁹.

This is an interesting association between schizophrenia and asthenic build and suggests that it is probably not genetics that makes individuals with schizophreniatend toward obesity but, rather, lifestyle and the medication they take.

Many attempts have been made to look for genes that predispose to antipsychotic-associated weight gain ³⁰, and that work continues.

There is little doubt that antipsychotic drugs are critical factors in the current widespread tendency to obesity of schizophrenia patients. A study of 51 patients with chronic schizophrenia who had never received antipsychotic drug treatment and 51 healthy comparison subjects showed that, despite the lifestyle issues referred to above, the drug-naive patients in the study had a significantly lower BMI (19.4) than the controls (22.7) ³¹. The authors of this study concluded that schizophrenia in the absence of antipsychotic drug treatment is not associated with obesity. The fact remains that almost all individuals diagnosed with schizophrenia do need to be treated with antipsychotic medication and essentially all antipsychotic medications increase weight ³², although some of the many available drugs have been more implicated than others ^{33, 34, 35, 36}. Large appetite increases are sometimes described.

 Example

The symptoms of a young male patient with severe schizophrenia improved remarkably when he was changed from a first generation depot antipsychotic to olanzapine 20 mg HS. He had been extremely emaciated (weighing 110 pounds) and apathetic, but, in two months, lost many of his psychotic symptoms, gained twenty pounds and become more active, riding his bicycle everyday. A few months after starting olanzapine, he missed his psychiatric appointment, calling in to explain from a surgical ward of a nearby hospital that he had broken his leg falling off his bike. “I get so terribly hungry,” he said, “that I fell off because I was rushing home – I just couldn’t wait to get something to eat.”

Antipsychotics are not the only psychotropic medications that induce weight gain. As mentioned earlier, many people with schizophrenia suffer from co-morbid depression ¹⁸ for which they are commonly treated with antidepressants and mood stabilizers, which also have weight-inducing potential ³⁷.

Circadian rhythms are responsible for daily food intake, hunger and satiety being under the control of a central pacemaker in the anterior hypothalamus. The core clock mechanism is linked to lipogenic and adipogenic pathways so that disruption of circadian physiology can lead to obesity by shifting food intake schedules ^{38, 39}. Meal times are potent synchronizers of biological clocks and the disrupted food intake of people with schizophrenia can be a cause (or a result) of disturbed rhythms ^{38, 39}.

Recent studies have shown that significant sleep/circadian disruption occurs in many if not most patients with schizophrenia ^{40, 41, 42, 43}. The disturbed sleep and lack of routines in eating predispose individuals with schizophrenia to disrupted lipid control that can lead to weight gain and obesity.

Immune mechanisms can lead to disturbances in glucose metabolism and in inflammatory response that can result in obesity, and this is of potential significance in schizophrenia ^{44, 45} because the most consistent association in genome-wide association studies (GWAS) of schizophrenia has been with the major histocompatibility complex (MHC) region of the genome, which contains hundreds of genes involved in immunity ^{46, 47}. There may be an active connection in schizophrenia patients between obesity and altered immunity.

The negative health consequences of high BMI are mediated by raised blood pressure, disturbances in glucose metabolism, and adverse lipid profiles ⁴⁸.

Obesity constitutes a major risk factor for type 2 diabetes, to which people with schizophrenia seem particularly prone (see genetic factors above). It has been found that, even in first-episode, drug-naïve patients with schizophrenia, 15% show impaired fasting glucose tolerance, are more insulin resistant and have higher levels of plasma glucose, insulin, and cortisol than healthy comparison subjects. This may be due to shared predisposing genes between schizophrenia and diabetes, or to the stress inherent in this illness ⁴⁹.

Obesity is a major factor in the metabolic syndrome ^{50, 51} and in cardiovascular problems ⁵², which considerably shorten the lives of people with schizophrenia ⁵³. Besides medical problems such as diabetes and metabolic syndrome and cardiovascular problems, obesity poses a risk for sleep apnea and impairs the quality of sleep ^{54, 55}. Obesity increases the risk of respiratory difficulties and, in women, leads to difficult pregnancy and labor. Obesity lowers the threshold for the development of many cancers through the secretion of estrogens, adipokines and cytokines by adipose tissue ⁵⁶.

There are also psychosocial sequelae of obesity in this population, for instance non-adherence to antipsychotic medication (in an attempt to prevent more weight gain), which can lead to symptomatic relapse and rehospitalization ⁵⁷. There also appears to be an unexplained positive correlation between obesity and impairment of neurocognitive function in schizophrenia ^{58, 59}. Obesity further impairs quality of life through increased physical and psychological problems as well as increased perceived stigma ^{60, 61, 62}.

Example

One young woman with schizophrenia lived with a boyfriend who came from a well-to-do family. Because she herself was alienated from her family and had essentially no close friends other than her partner, she especially looked forward to holidays when she was invited to her boyfriend’s family’s lavish parties. Her illness symptoms were stable, but, over time, she put on increasing amounts of weight. Her weight soared to 300 pounds and her boyfriend’s family, who had previously been very fond of her, stopped inviting her to parties – they told her boyfriend that they were ashamed for their other guests to see her.

The management of weight gain and obesity in patients with schizophrenia requires regular and frequent monitoring, early recognition, and multidisciplinary treatment ⁶³.

The strategies are essentially the same as they are in the general population ⁶⁴, with the added provisos that attempts at health promotion often do not reach this socially isolated population, that psychiatric patients may not regularly see a primary care provider for health screening and monitoring, that the motivation to change is low in this population, and that control of psychotic symptoms usually takes precedence, for both doctor and patient, over the need to keep weight down ^{65, 66, 67}.

There needs to be an emphasis on prevention through health promotion programs that focus on weight gain and its sequelae and on the urgency of tackling these issues early before metabolic changes ensue. This needs to be started in early intervention for psychosis programs ⁶⁸ although clinicians are loath to do so for fear of turning patients away from much needed medications. Health promotion for this population needs to be targeted and tailored ⁶⁹, embedded in healthy life style education that includes diet, exercise, and discontinuation of use of cigarettes and street drugs ⁷⁰. Despite the significant weight gain that comes after successful smoking cessation and the increase in diabetes and hypertension that comes with it, it remains of primary importance for patients with schizophrenia to stop smoking as this significantly decreases cardiovascular risk, the major factor in the high mortality rate in this population ⁷¹.

Screening and monitoring (waist circumference measures, weight, blood pressure, hemoglobin A1C) have to be conducted regularly and frequently ^{69, 72}, starting with first contact with psychiatric services.

Motivational interviewing to help motivate patients to change their behavior has been shown to be successful in schizophrenia with respect to weight reduction ^{73, 74}. It is a method that uses open-ended questioning and reflective statements that establish an empathic relationship between patient and counselor. Ambivalences and barriers to change are explored, personal feelings and opinions are solicited, up-to-date information is offered and, as a result, the motivation for change is facilitated. The approach is personalized so that preferences in foods and activities are emphasized ^{65, 75, 76}.

Example

The patient referred to above who was disinvited from her boyfriend’s family’s parties, refused to attend exercise programs because they were “too much work.” She loved dancing, however, and was happy to join a salsa class, which she attended regularly.

Behavioral interventions targeting calorie restriction (avoidance of high carbohydrate and high fat foods) and energy output (walking 20-30 minutes a day) work ^{77, 78, 79}, but they need to be personalized, with frequent face-to-face contact. And the providers need to be well trained ⁸⁰.

Because disrupted sleep contributes to weight gain, assuring sound sleep helps to combat obesity. Through its effects on circadian rhythms, or perhaps through other means of action, melatonin not only attenuates weight gain but also protects against metabolic syndrome in schizophrenia ^{81, 82, 83}.

Somewhat paradoxically, the weight-inducing drugs used to treat schizophrenia also tend to induce sedation, so that the results of drug switching are never certain.

Example

A young man with a schizophrenia diagnosis had been treated with olanzapine and had put on weight. For this reason, he was switched to aripiprazole, an antipsychotic drug that is a partial agonist and purported to help patients lose weight ^{84, 85} Unexpectedly, the patient gained even more weight. At the same time, his psychotic symptoms worsened so he was eventually placed on clozapine, a drug for non-responders, which is known to add weight. Paradoxically, he not only stopped gaining weight, but dropped thirty pounds in the ensuing six months. Apparently, while on aripiprazole, the patient had been up in the night eating whereas clozapine, which is sedative, made him sleep through the night.

Switching from a weight-inducing antipsychotic to one that is relatively weight-sparing is a common clinical strategy, but it is of uncertain benefit ^{86, 87}. Perhaps more important is to keep doses as low as possible and to avoid using more than one antipsychotic medication at a time. Adding metformin is another potentially useful strategy ^{63, 88, 89}.

Good prenatal care is critical in schizophrenia because of the potential effects of pregnancy on a genetically-at-risk fetus. Obesity during pregnancy is not uncommon in this population for all the reasons addressed earlier in this paper. Obesity during pregnancy leads to increased rates of gestational diabetes, pre-eclampsia, and difficult labors. Infants are at relatively high risk for congenital malformation and stillbirth. Mothers may experience post-partum hemorrhage. Children of obese mothers may, in later years, develop obesity and metabolic problems ^{90, 91}. Specific dietary advice is, therefore, required, during prenatal care and efforts made to ensure motivation to curb appetite and increase activity levels.

For gross obesity, bariatric surgery is a possibility. It was initially withheld from patients with schizophrenia because it was not known if these patients would be able to manage postsurgical protocols. More recently, it has been found that the success rate of bariatric surgery for people with schizophrenia is the same as it is in the general population ^{92, 93}.

Peer support and counseling have become part of standard care for schizophrenia on the assumption that individuals are most likely to change behavior if they identify with the counselor. Advice from peers who have gone through similar experiences can sound more credible than advice coming from health care providers. Peers who have experienced and overcome weight gain while maintained on the same medication as the person they are advising can be very powerful role models ^{94, 95, 96, 97}.

Whoever is providing advice, support, and encouragement, in the end, patients must be engaged in their own health care and learn to manage their own weight ⁹⁸. This holds true for patients with schizophrenia, but this population faces barriers to self-management that are greater than the difficulties faced by patients with other diagnoses. Certain symptoms of schizophrenia – apathy, social isolation, paranoia for example - make it difficult to engage patients in self-care. Schizophrenia patients also have knowledge barriers that can be attributed not only to isolation but also to cognitive deficits. They may be addicted to alcohol or drugs, which cloud consciousness and diminish motivation. The obesity may be of such magnitude that it poses functional barriers to activity of all sorts. Patients with schizophrenia often lack the support of friends and family and they may not be able to sustain good relationships with health care providers ⁹⁹.Nevertheless, it is possible for patients with schizophrenia to be motivated to take charge of both their physical and their mental health ¹⁰⁰.

Technology (Internet programs, email messaging, smart phones, use of pedometers) has proven very useful in the field of self-management ^{101, 102, 103, 104}. And people with schizophrenia have shown that they are not averse to using technology ^{105, 106}.

In many ways, it is more comfortable for many people with this diagnosis to interact with an appliance than with a person ^{107, 108}. Miller et al. ¹⁰⁹ found that, at the time their survey was done, 56% of their study participants, all diagnosed with schizophrenia, were using text messaging; 48% had an email account. Twenty seven percent used social media sites daily (Facebook being the most popular) and most of those who used the technology claimed that it increased their ability to socialize.